6,8-Dimethyl-7-ethoxycarbonyl-4-hydroxymethyl-1-phthalazone (hereinafter referred to as "Phthalazinol") is a compound disclosed in the specification of U.S. Pat. No. 3,963,716 (1976) as a medicine for preventing and/or treating cerebral blood vessel disorders such as cerebral hemorrhage, cerebral thrombosis and cerebral arteriosclerosis, peripheral blood vessel disorders such as obstructive arteriosclerosis, and nerval diseases such as spinocerebellar degeneracy, multiple sclerosis, muscular dystrophy and Parkinson's disease.
The inventors have found that though Phthalazinol is absorbed nearly completely (about 100%) when it is administered orally, it is readily metabolized and 4-hydroxymethyl group thereof is converted into inactive 4-carboxyl group by the metabolism with alcohol dehydrogenase in the living body before it arrives at the blood circulation system.
Phthalazinol subjected to the tests at present has a low absorption velocity and, therefore, though Phthalazinol is once absorbed, it is metabolized successively. Consequently, the actual Phthalazinol content of the blood is as small as several tenths of the theoretical value calculated on the assumption that Phthalazinol is not metabolized at all but completely absorbed in the blood.
This phenomenon is generally called "first pass effect".
The inventors hit upon an idea that in order to minimize the first pass effect and to increase the Phthalazinol concentration in the blood, the absorption velocity should be kept at a value far higher than the vanishing velocity thereof in the blood. The inventors further hit upon a good idea that the absorption velocity can be elevated and the Phthalazinol concentration in the blood can be increased by employing characteristic physical properties of Phthalazinol, namely a poor water-solubility (about 0.2 mg/ml. of water at 25.degree. C.) and a low wettability with water.
Generally, as methods of enhancing the absorption velocity of a difficultly water-soluble, difficultly wettable medicine, there may be mentioned the pulverization of the medicine into a fine powder and the addition of a surfactant. According to our experiments on the elution of Phthalazinol treated by the above methods, however, the elution could not be accelerated.
After intensive investigations from the viewpoint of enhancing the contact of Phthalazinol with water, the inventors have found that a composition prepared by adding a water-soluble cellulose ether to Phthalazinol or by adding a polyhydric alcohol to the above two compounds exhibits a remarkably improved elution of Phthalazinol as compared with that obtained by adding a surfactant to Phthalazinol. The present invention has been completed on the basis of this finding.